Salt(s) of 7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7h-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide and processes of making thereof

Abstract

This invention relates to (1) process of making 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide and salts thereof; (2) novel salt(s) of 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide; (3) pharmaceutical compositions comprising the same; and (4) methods of treatment using the same.

1 . Succinate salt of 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide. 
     
     
         2 . The salt of  claim 1 , wherein the salt is described by Formula (II) 
       
         
           
           
               
               
           
         
       
     
     
         3 . The salt of  claim 1  in a non-hydrate form. 
     
     
         4 . The salt of  claim 1  in a hydrate form. 
     
     
         5 . A pharmaceutical composition comprising:
 (a) a therapeutically effective amount of a salt according to any of  claim 1 ; and   (b) at least one pharmaceutically acceptable carrier, diluent, vehicle or excipient.   
     
     
         6 . A method of treating a disease which responds to an inhibition of cyclin dependent kinases activity comprising the step of administering to a subject in need of such treatment a therapeutically effective amount of a salt according to  claim 1 . 
     
     
         7 . A method of preparing the compound of Formula (I) comprising 
       
         
           
           
               
               
           
         
         (2) converting the 
       
       
         
           
           
               
               
           
         
       
     
     
         8 . The method of  claim 7 , wherein step (1) is performed in the presence of Pd(OAc) 2 , BINAP, and Cs 2 CO 3 . 
     
     
         9 . The method of  claim 7 , wherein step (2) is performed in the presence of HCl(aq.) and toluene. 
     
     
         10 . The method of  claim 7 , wherein the 
       
         
           
           
               
               
           
         
       
       is further converted to 
       
         
           
           
               
               
           
         
       
     
     
         11 . The method of  claim 10  where in the conversion takes place in the presence of IPA and 
       
         
           
           
               
               
           
         
       
     
     
         12 . A method of preparing the compound of Formula (III): 
       
         
           
           
               
               
           
         
       
       comprising converting 
       
         
           
           
               
               
           
         
       
     
     
         13 . The method of  claim 12 , wherein the conversion of the 
       
         
           
           
               
               
           
         
       
       takes place in the presence of MnO 2 , NaCN, 
       
         
           
           
               
               
           
         
       
       and THF. 
     
     
         14 . The method of  claim 12  wherein the 
       
         
           
           
               
               
           
         
       
       is formed from 
       
         
           
           
               
               
           
         
       
     
     
         15 . A method of preparing the compound of Formula (III): 
       
         
           
           
               
               
           
         
       
       comprising: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         16 . A method of preparing the compound of Formula (IV): 
       
         
           
           
               
               
           
         
       
       comprising 
       
         
           
           
               
               
           
         
       
     
     
         17 . The method of  claim 16  wherein the reaction takes place in the presents of n-BuOH. 
     
     
         18 . A method of preparing the compound of Formula (IV): 
       
         
           
           
               
               
           
         
       
       comprising: